This section is intended to introduce the reader to various aspects of the art that may be related to various aspects of the present invention. The following discussion is intended to should be understood that statements in the following discussion are to be read in this light, and not as admissions of prior art.
Heart failure is one of the most common causes of admission to the hospital in the world. Studies have shown that patients with dilated hearts have a reduction in the frequency of hospital admission and prolongation of life with the implantation of bi-ventricular pacemakers and automatic implantable cardiac defibrillators (AICDs). This benefit extends to patients with both ischemic and idiopathic cardiomyopathy. Recently, “piggybacking” technology onto AICDs and bi-ventricular pacemakers for sensing the progression of impending HF to reduce the number and length of stay of hospital admissions for congestive heart failure has been proposed.
There are two proposed “piggybacked” heart failure warning systems placed on bi-ventricular pacemakers and AICDs to reduce hospital admissions. First, Chronicle® measures right heart pressures in an attempt to monitor increases that are indicative of heart failure. Second, Optivol® uses lung impedance (conductance) measurements as an indication of pulmonary edema. However, both are downstream measures of what is anticipated to be an earlier indicator of impending heart failure—left ventricular (LV) preload or left ventricular end-diastolic volume (LVEDV). There are currently no proposed technologies that can perform chronic left ventricular volume measurements in part because implanted devices in the left heart lead to arterial embolism and stroke.
Conductance measurements have been available as an invasive tool to detect instantaneous left and right ventricular volume since 1981. Conductance tetrapolar electrodes are usually placed on a catheter located within the heart chamber to determine instantaneous volume. Conductance systems generate an electric field using a current source, and volume is determined from the returning instantaneous voltage signal. Conductance electrodes have not been previously placed on the LV epicardium to interrogate the LV blood volume. Further, the conductance technique is limited as the resulting volume measured is a combination of both blood and surrounding myocardium, while only the blood volume is desired. The current invention proposes the use of an admittance measurement system, to separate the blood and muscle components from the combined voltage signal to determine LV preload from previously implanted AICD and bi-ventricular pacemakers, for the first time.
Thus, “piggybacking” the admittance measurement system described herein onto previously implanted AICD and bi-ventricular pacemakers will serve as an early warning system for impending heart failure, superior to the current approach of measuring right heart pressure and lung impedance (conductance).
LV preload determination: LV preload may identify impending congestive heart failure in patients before increases in lung impedance (conductance) and right heart pressures occur. When the chronic canine model of congestive heart failure is acutely exposed to increases in afterload, an elevation of left but not right heart filling pressures has been shown to occur.
FIG. 1 is a bi-plane left ventriculogram from a patient with congestive heart failure and a previously implanted AICD/bi-ventricular pacer demonstrating how the leads span the LV blood from the lateral left ventricular epicardium to the right ventricular septum, and as an alternative configuration, from the lateral left ventricle to the right atrium (RA). These two lead configurations to be investigated are demonstrated in FIGS. 2a and 2b. 
FIGS. 2a and 2b show two electrode configurations and include (a) LV septum to LV free wall, and (b) right atrium (RA) to distal LV free wall.
LV preload as the standard for impending heart failure: The backward heart failure concept was first proposed in 1832, and contends that when the LV fails to discharge its contents, blood accumulates and pressures rise in the atrium and venous system emptying into it. The inability of the LV to shorten against a load alters the relationship between end-systolic pressure and volume so that LV end-systolic volume rises. The following sequence then occurs, which at first maintains cardiac output, but ultimately leads to clinical deterioration—(a) LV end diastolic volume and pressure increase, (b) the volume and pressure rise in the left atrium, (c) the left atrium contracts more vigorously (Starling's Law), (d) the pressure in the pulmonary veins and capillary beds behind the LV rise, (e) transudation of fluid from the pulmonary capillary beds into the pulmonary interstitial space increases, (f) the elevation of LV, left atrial, and pulmonary venous pressures results in backward transmission of pressures into the pulmonary arterial circuit and leads to pulmonary hypertension, and finally, (g) right heart failure then occurs as a consequence of left heart failure.
Further, as the LV fails, it will remodel to accommodate the increased load, to reduce chamber pressures. Increased LV preload is more easily detected than pressure elevation since the diastolic pressure-volume relation is relatively flat and produces a larger change in volume for a given change in pressure. This relationship is more evident as the LV remodels and dilates since the diastolic ventricular pressure-volume relation flattens in heart failure. An increase in preload will also antedate an elevation in right heart systolic pressures, due to the length-tension relationship of cardiac muscle, i.e., —muscle is stretched before generating greater systolic pressures. Based on these additional arguments, the principal investigator and colleagues anticipate that increasing LV preload will be the most sensitive measure of impending congestive heart failure.
Right heart pressure measurement: The Chronicle® device utilizes a pressure sensor placed on the right ventricular lead to detect when there is an increase in right heart pressures to warn of impending congestive heart failure. The device has been validated against invasive fluid filled pressure sensors up to 1 year, in a variety of positions (supine and sitting) and activities (valsalva and exercise). Pressure increases have been shown to occur in 9 of 12 patients proceeding hospitalization for congestive heart failure, and there was a trend in fewer heart failure admissions with the pressure monitoring intervention compared to a control group in the COMPASS-HF study.
However, there are many concerns regarding using right heart pressures to monitor for impending heart failure. The major concern is that right heart failure is downstream of left heart failure and pulmonary edema, and based on physiologic principles, will be a less robust measure. Evidence of this concern is that Chronicle® was only able to detect 9 of 24 events that were treated with the adjustment of heart failure medications to avoid hospitalization. Second, the device was reviewed by the FDA in February 2007, and approval was not granted based on the COMPASS-HF study due to statistically non-significant results between right heart pressure and control arms. Third, the device requires correction for varying ambient atmospheric pressure with an external device that records ambient barometric pressure.
Left atrial pressure measurement: There are currently two groups developing implantable left atrial (LA) pressure sensors to warn of impending congestive heart failure. The first is Savacor which has developed HeartPOD™ sensor, and is currently engaged in the Homeostasis 1 Clinical Trial. The second group is a collaboration between Virginia Commonwealth University and Vital Sensors based in Richmond, Va.
The concern regarding this technology is that there have been patients in the Homeostasis 1 Clinical Trial who have had strokes, due to the presence of a pressure sensor implanted on the LA side of the intra-atrial septum. In contrast, our approach of using epicardial Admittance does not implant an intra-cardiac foreign device in the left heart chambers, and thus there is no increased risk of stroke.
Lung impedance (conductance): The Optivol® is implemented in the InSync Sentry pacemakers made by Medtronic, Inc. The operating principle involves showing when the fluid index has passed a certain threshold from baseline, thus showing an increase in “lung wetness”. OptiVol uses a trans-thoracic resistance measurement from the tip of the RV AICD lead to the case of the battery pack for the pacemaker/defibrillator, and thus provides a wide electric field including the LV, LA, thoracic skeletal muscle, ipsilateral lung tissue, intravascular lung volume, and finally pulmonary interstitial edema to measure a changing fluid index.
When Optivol® was initially investigated in 33 patients, a promising 77% sensitivity with only 1.5 false-positive per year were described. However, a larger series of 373 patients revealed a less impressive sensitivity of 60% for heart failure detection, with a positive predictive value of 60% as well. The explanation for the decreasing sensitivity and positive predictive value of Optivol® is consistent with the wide variety of tissues being interrogated by the electric field. For instance, factors that would decrease the impedance measurement include pulmonary interstitial congestion (the only true endpoint), increased myocardial mass, increased intra-vascular blood volume, pulmonary effusions, and edema near the AICD pocket. In contrast, factors that would increase and thus reduce the sensitivity of the impedance measurement include alterations in pulmonary tissue due to heart failure, which include increased small airway resistance, increased air volume in the lung, previous smoking with COPD, increased lymphatic drainage, and reduced skeletal muscle mass as part of cardiac cachexia. Finally, since the authors of this patent application anticipate that increased pulmonary interstitial edema occurs following increased LV end-diastolic volume, a pure measure of LV preload will achieve more favorable sensitivity and specificity of heart failure detection. Currently no such device exists.
A second criticism is that Optivol® utilizes state-of-the-art conductance-to-volume equations which assume the distance between the stimulation and voltage sensing electrodes are constant. This is not the case with Optivol®, where the RV AICD lead electrodes are in motion as a source electrode with the relatively stationary AICD generator. Thus, Optivol® is currently being used for measurements where the independent electrodes may have arbitrary, time-dependent distances from one another. However, the implications of violating Baan's assumptions which assume fixed electrode positions have not been addressed. This raises the question of the sensitivity of the measurement to electrode positioning. The new approach proposed in the current application is based upon motion of source and sink electrodes and can be used to improve the accuracy of the Optivol® approach.
Inadequate traditional conductance measurements: Traditionally, volume measurements are made by determining the time dependent (as the heart beats) value of conductance using a catheter placed in the left ventricle. The original theory was proposed by Jan Baan in 1981 and relates conductance to volume through a simple equation based on stroke volume, resistivity of blood, and the length between the voltage contacts of the catheter.
      Volume    =                            ρ          ⁢                                          ⁢                      L            2                          α            ⁢              (                              G            blood                    -                      G            II                          )              ,where ρ represents the resistivity of blood, L represents the fixed length between the voltage contacts, α is constant dependent on the stroke volume (Baan assumed it to be 1), Gblood is the conductance of blood, and G∥ is the muscle conductance in parallel with the blood.
There are several criticisms of this traditional method. The first is that the relationship between blood conductance and volume is not linear, as shown in the literature, and as implied by the non-uniform shape of the stimulating field. Second, the measurement not only extends into the blood pool, but also into the surrounding tissues (such as the myocardium). This implies that the measurement will artifactually increase the volume because the catheter will see further than only the blood pool. The correction for the parallel Z conductance G∥ is a calculated constant in the above equation, but the parallel conductance is known to be time-varying. The accepted methods for conductance measurement are outdated in this matter. For example, the Fick method is used with the Conductance technique to measure the steady state parallel conductance using a hypertonic saline bolus injection. The value derived from this measurement is a constant, and is not time dependent. Thus, there is a need to mature this approach to separate the blood and muscle components of the signal. The authors of this patent application are the first to develop a real-time method to distinguish between blood and muscle components using admittance measurements.
FIG. 3a shows incomplete traditional conductance circuit approach that models both cardiac muscle (Gm) as real or conductive components only. FIG. 3b shows a circuit model including the imaginary or capacitive properties of cardiac muscle.
Finally, the volume-conductance equation is modeled after an incomplete circuit (FIG. 3a). Measurements were considered all real because only the magnitude was measured. However, such an approach ignores the imaginary or capacitive properties of cardiac muscle (FIG. 3b), and thus separating blood and muscle is difficult and done incorrectly using this traditional approach.
Moreover, currently, there are no heart failure warning systems which can detect the left ventricular volume or left ventricular diameter, since any instrumentation placed within the left heart would lead to clot formation and a subsequent stroke. A technique has been developed to piggyback electrodes onto the surface of the heart to mitigate against the risk of stroke, while still determining when the left ventricle begins to dilate as a means to warn of impending heart failure. For this device to be effective, the patient and doctor need a technique to allow the left ventricular volume and/or diameter information to be transmitted. One such technique would be telemetry—a technology that allows remote measurement and reporting of information on the left ventricular volume or diameter, or a change in left ventricular volume of diameter from baseline. Remote reporting of this information will allow the patient to report this information to his/her doctor from a site other than the physician's office, such as home.